Hydrate drug substance physical stability

Confirmatory studies should be conducted on both the drug substance and the final formulation as part of the formal stability studies for registration, and may be regarded as an accelerated stability test (2). It is very important that the physical state of the sample be in its manufactured and / or marketed form (i.e., final crystal form, particle size, and hydration state) during exposure. Techniques used to alter the physical state of the sample (e.g., such as grinding to reduce particle size) as recommended in some publications (7) should be avoided. 

Some new drug substances exist in different crystalline forms that differ in their physical properties. Polymorphism may also include solvation or hydration products (also known as pseudopol5rmorphs) and amorphous forms. Differences in these forms could, in some cases, affect the quality or performance of the new drug products. In such cases, the bioavailabUity stability can be altered requiring choice of specific stable solid dosage forms. 

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